Evidence is now available that mineralocorticoids react with a nuclear receptor system to initiate the action on active sodium transport. Recent attempts to isolate and purify the receptors have been frustrated by the lability of the steroid-protein complex and the fragility of the receptor proteins. The most promising means of circumventing these difficulties would be to synthesize site-specific steroids which would bind covalently to the receptors. To convert a hormone into an agent capable of selectively alkylating the hormonal receptor, it is necessary to attach an alkylating function to the molecule at such a position that the extra bulk does not hinder the binding of the hormone analog to the receptor. Diazoketones are of particular interest because they can be transformed into an excited state by means of irradiation after they have bound to the receptor--thus an especially selective means of alkylation is, in principle, possible. In the present work 21-diazo-21-deoxycorticosterone derivatives are used to bind selectively to corticosteroid receptors. Photolysis with light at 255 nm gives a covalently labeled receptor. The synthesis of radiolabeled diazoketones provides a means of detecting the labeled protein. The methods of protein purification (isoelectric focusing and gel electrophoresis) will be applied to the labeled receptor in order to isolate, purify and sequence these materials.